Linker Information
General Information of This Linker
| Linker ID |
LIN0PBTHS
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| Linker Name |
Mc-Ala-Ala-Ala
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| Linker Type |
Cathepsin-cleavable linker
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| Antibody-Linker Relation |
Cleavable
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| Structure |
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| Formula |
C19H28N4O7
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| Isosmiles |
O=C(O)[C@@H](NC([C@H](NC([C@@H](NC(CCCCCN1C(C=CC1=O)=O)=O)C)=O)C)=O)C
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| InChI |
InChI=1S/C19H28N4O7/c1-11(17(27)21-12(2)18(28)22-13(3)19(29)30)20-14(24)7-5-4-6-10-23-15(25)8-9-16(23)26/h8-9,11-13H,4-7,10H2,1-3H3,(H,20,24)(H,21,27)(H,22,28)(H,29,30)/t11-,12+,13-/m0/s1
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| InChIKey |
UCOOONSXCROXON-XQQFMLRXSA-N
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| Pharmaceutical Properties |
Molecule Weight
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424.454
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Polar area
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161.98
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Complexity
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677.5499552
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xlogp Value
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-0.9295
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Heavy Count
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30
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Rot Bonds
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12
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Hbond acc
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6
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Hbond Donor
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4
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Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
IMGC-936 [Phase 1/2]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT04622774 | Clinical Status | Phase 1 | ||
| Clinical Description |
A phase 1/2, first-in-human, open-label, dose-escalation and expansion study of IMGC936 (Anti-ADAM9 antibody drug conjugate) in patients with advanced solid tumors.
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| Primary Endpoint |
During dose escalation measure incidence and severity of Treatment Emergent Adverse Events, During dose escalation characterize dose-limiting toxicities (DLTs), During expansion describe the overall response rate.
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| Other Endpoint |
During dose escalation and expansion to characterize study drug concentration and the concentration of anti-drug antibody, During dose expansion describe the duration of response and progression free survival, During dose escalation to describe the objective response rate and duration of response, During dose expansion measure incidence and severity of Treatment Emergent Adverse Events.
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| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Patients Enrolled |
Inclusion: Adults (≥18) with relapsed/refractory metastatic NSCLC (1-4 prior lines), TNBC (1-4 lines), CRC/GE/pancreatic cancer (1-3 lines), ECOG 0-1, adequate organ function (ANC≥1.5K/uL, platelets≥75K/uL, ALT/AST≤3×ULN, eGFR>30mL/min). Exclusion: Active CNS/ocular/cardiovascular disease (LVEF<50%, QTc>480ms), recent anticancer therapy (4w systemic/6w radiation), uncontrolled infections (HBV/HCV/COVID-19), or live vaccinations within 4w. Contraception required for 28w post-treatment.
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| Administration Dosage |
Participants received IMGC936 0.5, 1.0, 2.0, 4.0, 5.0, 6.0, 7.0 milligrams (mg)/kilogram (kg) via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter.
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| Related Clinical Trial | |||||
| NCT Number | NCT04622774 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description |
A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation and Expansion Study of IMGC936 (Anti-ADAM9 Antibody Drug Conjugate) in Patients With Advanced Solid Tumors
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| Primary Endpoint |
Primary endpoints include TEAEs/SAEs monitoring (up to 3 years) and DLT assessment per CTCAE v5.0 (Cycle 1: 21/28 days) with hematologic/non-hematologic criteria including Grade 4 neutropenia/thrombocytopenia, ≥Grade 3 ocular/hepatic events, and Hy's law cases. Dose expansion phase evaluates ORR per RECIST v1.1 (CR: complete lesion disappearance; PR: ≥30% target lesion reduction).
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| Other Endpoint |
Secondary objectives comprise PK analysis (Cmax), ADA incidence, ORR/DOR/PFS per RECIST v1.1 (PD: ≥20% target lesion increase +5mm absolute growth), and safety monitoring (TEAEs leading to discontinuation). DOR/PFS analyzed via Kaplan-Meier method.
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References